Regenerative medicine in the treatment of specific dermatologic disorders: a systematic review of randomized controlled clinical trials

Aims and objectives The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study. Method Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events. Results In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte–keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP. Conclusion Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study.


What is already known about this topic?
• Regenerative medicine is an effective treatment method for managing inflammatory and degenerative diseases, including inflammatory skin diseases.• Regenerative medicine methods encompass therapeutic approaches such as PRP injection, SVF injection, use of conditioned medium, autologous melanocyte and keratinocyte cell transplantation, exosomes, utilization of mesenchymal stem cells, and a combination of the aforementioned methods.• So far, most studies on the role of regenerative medicine in dermatology have focused on rejuvenation, scar healing, and wound healing.However, there has been no systematic review of specific skin diseases.

What does this study add?
• To date, clinical trial studies in the field of regenerative medicine for the treatment of specific dermatologic diseases such as androgenetic alopecia (AGA), vitiligo, alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa have been conducted.• In relation to AGA, 86.2% of the studies have shown the effectiveness of various regenerative medicine methods in treating the disease.This rate is 100% for vitiligo, 83.3% for alopecia areata, 100% for melasma, 50% for LSA, 100% for acne vulgaris, 100% for chronic telogen effluvium, 100% for erosive oral lichen planus, and 100% for dystrophic epidermolysis bullosa.• The most common diseases associated with the use of regenerative medicine in their treatment include androgenetic alopecia and vitiligo.The most common methods in AGA include PRP, Conditioned Media, and a Combination of PRP and Basic Fibroblast Growth Factor (bFGF), respectively.Regenerative medicine has been effective in treating AGA up to 68.4% in studies.• In the case of vitiligo, the most common methods are

Introduction
Regenerative medicine is a crucial field of medicine known for its effectiveness in treating numerous inflammatory and degenerative diseases.This treatment approach encompasses various methods such as plateletrich plasma (PRP), stromal vascular fraction (SVF), conditioned media, and the transplantation of autologous epidermal melanocyte/keratinocyte cells [1][2][3].
These methods, through multiple pathways, ultimately lead to a singular result, which is the reversal of the inflammatory and degeneration processes by releasing cell factors and cytokines as well as promoting the proliferation of stem cells.For instance, the PRP injection method aims to release factors from concentrated platelets, whereas in the SVF injection, stem cells and factors derived from adipocyte cells stimulate cell regeneration [4,5].
In our study, we conducted a systematic review of all regenerative medicine treatment methods for primary skin diseases.Specifically, we focused on randomized controlled clinical trials to assess recovery rates, side effects, and intervention protocols.We meticulously analyzed each treatment method to provide a comprehensive summary of their efficacy in managing various skin conditions.

Inclusion and exclusion criteria
The inclusion criteria were specifically designed to include RCTs that investigate the effectiveness of regenerative medicine interventions for treating dermatological disorders.The exclusion criteria targeted studies that deviated from the RCT design, such as non-randomized trials, review articles, studies focusing on secondary skin lesions (e.g., scars, ulcers), and interventions not categorized under regenerative medicine (e.g., topical treatments, traditional pharmacotherapy).Additionally, non-human research (including animal models and in vitro studies), experimental studies, and trials lacking definitive outcome measures were excluded.Articles not written in English or those without accessible full texts were also omitted.

Study selection and data extraction
Two evaluators [A.J. and H.K] reviewed the titles and abstracts of identified records based on the predefined inclusion criteria.They assessed each study for various attributes, including the study design, the dermatological condition being assessed, the type of regenerative therapy, the treatment regimen, observed improvements, and reported adverse events.Details such as average age, gender distribution, and the number of participants were also collected from these studies.

Result
In our initial search, we obtained 458 articles.Based on the inclusion and exclusion criteria, we selected 65 articles to extract the final data.The screening steps are shown in the PRISMA chart (Fig. 1).The data extracted from the selected studies are presented in Table 2.In a total of 64 studies, 2888 patients with dermatologic diseases were examined.Among them, 1086 were women (44.8%) and 1339 were men (55.2%).However, in 12 studies (18.2% of the studies involving 463 patients), the separation of gender was not conducted.
Among the 64 studies conducted, there were a total of 149 intervention groups, with 102 groups treated using regenerative medicine methods.The following information provides the number and percentage of utilization for each regenerative medicine method: • Platelet-rich plasma (PRP) injection in 57 groups (55.9%).Adverse events were reported in 29 studies (45.3%), with the most common side effect being pain during the procedure.All side effects mentioned in the studies were mild, and no serious or life-threatening side effects were reported.

Androgenetic alopecia (AGA)
Of the 2888 patients included in the study, 1190 patients (41.2%) were diagnosed with AGA and received interventions.The most commonly used regenerative medicine method in this group was PRP, which was utilized in 36 intervention groups (from 23 studies).Among 23 studies, significant effectiveness of PRP compared to the control group has been proven in 19 studies, with no significant difference reported in the remaining 4 studies.
Additionally, the combination of PRP and Basic Fibroblast Growth Factor (bFGF), as well as Conditioned Media, were used in two intervention groups each (2 studies on conditioned media and one study on the combination of PRP and bFGF).Concentrated Growth Factor (CGF), Adipose-Derived Stem Cell constituents' extract, and preserving hair grafts in PRP were each studied in one group and one study.

PRP
In several studies, the effectiveness of PRP in treating AGA has been reported.Monthly intradermal injections of PRP for three months, on average, resulted in an   increase of 33.6 hairs in the treated area, while the placebo area experienced a decrease of 3.2 hairs.The PRPtreated group showed a significant difference in hair density compared to the placebo group, with an increase of 45.9 hairs per square centimeter versus a decrease of 3.8 hairs per square centimeter.Moreover, the density of terminal hairs increased by 40.1 hairs per square centimeter in the PRP-treated group, which was significantly different from the control group.However, there was no significant difference in the density of vellus hairs compared to the placebo group [2].
In another similar study, PRP injections at one-month intervals for three months improved average hair density by 71.1 hairs per square centimeter in the PRP-injected area, while the placebo group experienced a decrease of 26.7 hairs per square centimeter.By the end of the eighth week, the PRP-treated group showed a density improvement of 105.9 hairs per square centimeter, contrasting with a reduction of 52.4 hairs per square centimeter in the placebo group.This difference remained significant between the two groups [5].
In another study, the effectiveness of three monthly PRP injections was compared to a placebo.The results confirmed a significant improvement in anagen hair (67.6 ± 13.1), telogen hair (32.4 ± 13.1), and hair density (179.9 ± 62.7).Additionally, there was an improvement in the density of terminal hair, which was found to be 165.8± 56.8 [19].Treatment with PRP for four sessions at three-week intervals led to a significant improvement in hair density during weeks 12 and 24 following the treatment.It is noteworthy to mention that in the placebo group, a significant difference in hair density compared to the intervention was only observed during week 24 [20].
In a study where patients underwent five sessions of PRP treatment within eight weeks and were evaluated eight weeks after the last treatment session, the intervention group showed an average hair density increase of 12.76%, while the placebo group reported a hair density increase of only 0.99%.This significant difference between the two groups indicates the effectiveness of the intervention.However, it is worth noting that hair caliber decreased in both groups [21].Additionally, in other studies, significant effectiveness of PRP has been demonstrated compared to control groups and standard treatments [22][23][24][25][26][27][28][29][30][31][32][33][34][35] (Table 2).
However, it is important to note that in several studies, no significant response has been reported after PRP treatment.For example, PRP injection twice with a onemonth interval did not cause significant differences compared to the placebo group [36].Similarly, injections with intervals of one month for three sessions led to improvement in hair density, but did not show a significant difference compared to the placebo group [37].These results have been repeated in other studies where PRP injection, while controlling hair loss and increasing hair thickness and regrowth in some patients, did not cause a significant difference compared to the placebo group [38].
Another similar study, in which patients underwent five sessions of PRP with a 4-6 week interval and were evaluated one month and six months later, showed no significant difference in the number of hairs, hair diameter, and patient satisfaction between the intervention and control groups [39].

Combination of PRP and basic fibroblast growth factor (bFGF)
In the single study examining the use of both PRP and basic fibroblast growth factor (bFGF) in treating AGA, the findings demonstrated a notable enhancement in the group that received this combination alongside 5% topical minoxidil, in contrast to the group that only received the PRP and bFGF combination.Moreover, there was a significant improvement seen in the group treated with the PRP and bFGF combination compared to the group solely using 5% topical minoxidil.The average increase in hair count was approximately 31.28 hairs in the PRP group, 11.32 hairs in the minoxidil group, and 41.96 hairs in the combined therapy group (p < 0.05) [40].

Conditioned media
In both studies investigating the use of adipose-derived mesenchymal stem cell-conditioned medium in AGA treatment, a significant improvement has been demonstrated compared to the control group in terms of the percentage increase in Hair Count (184.9%),Hair Density (185.0%),Terminal rate (43.4%),Mean thickness (50.0%), and Total follicular units (104.3%).The studies also showed the highest decline in Vellus rate (− 56.0%) [6,41].

Adipose-derived stem cell constituents' extract
In the only study investigating the effectiveness of adipose-derived stem cell constituents extract (ADSC-CE) in the treatment of AGA, a significant improvement in hair count, hair density in the 8th week of treatment, and hair diameter in the 16th week was reported compared to the control group.A 19.2% increase in hair count and a 21% increase in hair density, contrasting with the control group, were observed [42].

Concentrated growth factor (CGF)
In the only study investigating the effectiveness of concentrated growth factor (CGF) in the treatment of AGA, the results showed a significant improvement in hair density, the ratio of terminal hairs to vellus, and the amount of hair growth compared to the control group.Furthermore, the satisfaction level of patients in the group receiving the combination of minoxidil and CGF was reported as 75% [43].

Preserving hair grafts in PRP
In the only study investigating the preservation of hair grafts using PRP to enhance hair transplantation results, the findings showed a substantial increase in hair density within the PRP group compared to the control group over a 6-month period.All patients demonstrated over 75% hair growth [44].

Vitiligo
Out of the 2888 patients included in the study, 1087 patients (37.6%) were diagnosed with vitiligo and underwent interventions.The most commonly used regenerative medicine method in this group was the transplantation of autologous epidermal melanocyte/ keratinocyte cells, which was employed in 19 intervention groups from 13 studies.In all 13 studies investigating the transplantation of autologous epidermal melanocyte/ keratinocyte cells, a significant improvement in clinical response was reported.
Subsequently, PRP was utilized in 8 intervention groups across 4 studies.Isolated melanocyte transplantation was employed in 6 intervention groups across two studies.Cell transplantation originating from hair follicles was utilized in 5 intervention groups across 3 studies (including 2 joint studies with the transplantation of autologous epidermal melanocyte/keratinocyte cells).Melanocyte-keratinocyte suspension in PRP was employed in 2 intervention groups across 2 studies (both studies were conducted in conjunction with the transplantation of autologous epidermal melanocyte/keratinocyte cells).Lastly, combined cell transplantation with both epidermal and hair follicle origins was utilized in a single intervention group in a study (a joint study with the transplantation of autologous epidermal melanocyte/ keratinocyte cells).

Transplantation of autologous epidermal melanocyte/ keratinocyte cells
In a study comparing cell transplantation from grafts with a size of 1/3 of the recipient area, with a cell count of 231.60 ± 27.03 melanocytes per square millimeter, to grafts with a size of 1/5 of the recipient area, with a cell count of 154.90 ± 27.65, the amount of repigmentation and color match in the first group were significantly better than in the second group.However, the time of the onset of repigmentation was not significantly different between the two groups [3].
In a study comparing two methods of suspending autologous epidermal melanocyte/keratinocyte cells and grafting through suction blister, both groups demonstrated significant improvement.However, the transplantation through suspension showed a more remarkable improvement compared to the suction blister group (p = 0.002).An excellent response was observed in 71% of lesions in the epidermal melanocyte/keratinocyte group, while only 27% of the lesions in the suction blister group exhibited such a response [8].
Regarding the preparation of the recipient site of autologous epidermal melanocyte/keratinocyte cells, site preparation with Erbium YAG laser has resulted in 54.7% repigmentation, while preparation with motorized dermabrasion has led to 48.8% repigmentation; both methods show significant improvement.However, no significant difference was observed between the two groups [45].
Also, in the comparison of the preparation of the receptor site between fractional CO 2 and full surface CO 2 methods, excellent repigmentation was observed in 40% and 35% of patients, respectively.Despite the significant improvement in both groups, no significant difference has been noted between the two groups [46].Furthermore, in the comparison of the two methods of dermabrasion and microneedling at the transplant site, both methods have shown effectiveness.However, dermabrasion has demonstrated significant improvement compared to microneedling [47].

PRP
In all four studies investigating the effectiveness of PRP in treating vitiligo, significant improvement has been observed.In one study, the combination of excimer laser and PRP resulted in a significant improvement compared to each method alone.Additionally, in this study, excimer laser was significantly more effective than PRP in healing lesions [56].In another similar study, the combination of excimer laser and PRP was significantly more effective than excimer laser alone [57].
In a study comparing PRP, fractional CO 2 laser, the combination of these two methods, the combination of fractional CO 2 laser and UVB, and the combination of PRP, fractional CO 2 laser, and UVB in the treatment of vitiligo, the results showed a significant difference in the rate of recovery in all aforementioned groups compared to the control group.However, there was no significant difference between the intervention groups [58].
In a study comparing fractional CO 2 laser and PRP, the combination of the two, and the combination of fractional CO 2 laser and UVB in the treatment of vitiligo, the results demonstrated the superiority of the combination of fractional CO 2 laser and PRP, followed by the combination of fractional CO 2 laser and UVB, and finally fractional CO 2 laser and PRP individually.These differences were found to be significant [59].

Isolated melanocyte transplantation
In both studies investigating isolated melanocyte transplantation for the treatment of vitiligo, significant improvements were observed in the lesions.
In one study, melanocyte suspension in the individual's own serum was compared with melanocyte suspension in normal saline for the treatment of vitiligo.The results showed a significant improvement in both methods, with the first group showing a significantly greater improvement than the second group [60].
In another study evaluating melanocyte transplantation for the treatment of vitiligo, patients were divided into four groups.The first group received melanocyte transplantation and underwent 20 sessions of UVB before transplantation.The second group underwent transplantation and received 30 sessions of UVB after transplantation.The third group received 20 sessions of UVB before transplantation and 30 sessions of UVB after transplantation.The fourth group only underwent transplantation.
The results demonstrated a significant improvement in groups 1 to 3 compared to group 4. Additionally, there was a significant improvement in group 3 compared to groups 1 and 2. However, there was no significant difference in the amount of improvement between groups 1 and 2 [61].

Cell transplantation originating from hair follicles
In all three studies investigating the effectiveness of cell transplantation with hair follicle origin for the treatment of vitiligo, significant improvement has been observed in the lesions.
In a study examining three methods for cell transplantation with hair follicle origin in vitiligo treatment-using trypsin and collagenase, using trypsin alone, and using dermabrasion alone-the results showed a significant improvement in the first method compared to the third method.However, no significant difference was observed between the first and second methods, as well as between the second and third methods [62].
In two studies comparing cell transplantation with hair follicle origin and autologous epidermal melanocyte/keratinocyte cell transplantation for improving vitiligo lesions, both methods resulted in significant improvement.However, there was no significant difference in the degree of improvement between the two methods [53,54].

Melanocyte-keratinocyte suspension in PRP
In two studies comparing the transplantation methods of Melanocyte-keratinocyte suspension in PRP and the usual melanocyte/keratinocyte suspension, both methods demonstrated significant improvement.In one study, there was a significant improvement reported in the Melanocyte-keratinocyte suspension in PRP method compared to the usual melanocyte/keratinocyte suspension [50], while the second study reported no significant difference between the two groups [51].

Combined cell transplantation with both epidermal and hair follicle origins
In a study comparing the combination of two methods-transplantation of autologous epidermal melanocyte/keratinocyte cells and cell transplantation with hair follicle origin-with transplantation of autologous epidermal melanocyte/keratinocyte cells alone, the results showed a significant increase in repigmentation amount, speed, and color match in the first group compared to the second group [52].

Alopecia areata
Out of the 2888 patients included in the study, 332 patients (15.9%) were diagnosed with alopecia areata and received interventions.The most commonly utilized regenerative medicine method in this group was PRP, which was used in all seven intervention groups across six studies.
Out of the six studies examining PRP in the treatment of alopecia areata, five studies reported a significant improvement with it, while one study indicated no significant difference in the amount of improvement compared to the control group.

PRP
In three studies comparing PRP and triamcinolone acetonide injection for healing lesions, both methods showed significant improvement.However, in two studies, triamcinolone demonstrated greater improvement compared to PRP [63,64], while in one study, PRP showed significant improvement compared to triamcinolone [65].
In a study comparing three methods of PRP, including PRP injection, the combination of fractional CO 2 laser and PRP, and the combination of PRP and microneedling for lesion healing, all three methods demonstrated significant improvement, without any notable differences among them [66].
Furthermore, in a study comparing PRP and topical minoxidil 5% for the treatment of alopecia areata, both groups exhibited significant improvement, with PRP showing a significantly faster response in the beginning of hair regrowth [67].
Also, in a study that compared 3 sessions of PRP injections with a one-month interval to normal saline injections for the treatment of alopecia areata, the results showed a decrease in the severity of the disease by 9.05% in the PRP group and 4.99% in the normal saline group.There was no significant difference [10].

Melasma
Out of the 2888 patients included in the study, 90 patients (3.1%) were diagnosed with melasma and received interventions.The most commonly utilized regenerative medicine method in this group was PRP, which was used in two intervention groups across two studies.Additionally, the topical use of umbilical cord as a source of mesenchymal stem cells has been evaluated in an intervention group through a study.

PRP
In both studies investigating the effectiveness of PRP in improving melasma, the results showed a significant difference in the improvement rate compared to the control group.In the first study, the changes in the mean melanin level and mean mMASI score in the group receiving PRP for 4 sessions with a 2-week interval were significantly higher than those in the group receiving normal saline [68].In the second study, the results indicated a good response in 53.3% of patients receiving the combination of hydroquinone and PRP compared to 27% of patients receiving hydroquinone alone, and this difference was statistically significant [12].

Topical use of umbilical cord as a source of mesenchymal stem cells
In the only study that used umbilical cord as a skin mask rich in mesenchymal stem cells, the results demonstrated a significant improvement compared to the control group.The MASI score showed a decrease of 4.23 points in the intervention group and a decrease of 0.16 points in the control group, and this difference was statistically significant [69].

Lichen sclerosis et atrophicus (LSA)
Of the 2888 patients participating in the study, 69 patients (2.4%) were diagnosed with LSA and received interventions.Among the studies, PRP was investigated as an intervention in one study, and PRP and SVF were investigated as interventions in another study.

PRP
The only study examining PRP in the treatment of LSA found no significant improvement in the intervention group compared to the control group.The changes in the clinical scoring system for vulvar lichen sclerosus (CSS) in the group receiving PRP were -7.74, while in the placebo group they were -9.44.These changes were not significant between the two groups [14].

SVF
In a study comparing the combination of SVF and PRP to SVF alone, both methods were found to be significantly effective in healing lesions, but no significant difference was observed between the two groups [70].

Inflammatory acne vulgaris
Out of the 2888 patients included in the study, 30 patients (1%) were diagnosed with inflammatory acne and received interventions.The only modality investigated in this group was PRP injection.

PRP
The only study conducted on regenerative medicine in the treatment of inflammatory acne focused on comparing PRP and Long Pulsed Nd YAG Laser.The results showed significant effectiveness of both methods in reducing active acne lesions.However, no significant difference was observed in the healing of lesions between the two groups.In the group treated with PRP, a 58.77% reduction in the number of inflammatory acne lesions was seen [13].

Chronic telogen effluvium
Out of the 2888 patients included in the study, 30 patients (1%) were diagnosed with chronic telogen effluvium and received interventions.The only modality investigated in this group was PRP injection.

PRP
The only study conducted on regenerative medicine in the treatment of chronic telogen effluvium focused on comparing two methods of PRP (platelet-rich plasma) preparation.The first method involved preparing PRP using a centrifuge at 3500 rpm for 10 min, while the second method utilized a centrifuge at 1000 rpm for 10 min.
The results demonstrated the significant effectiveness of both methods in controlling hair loss, increasing hair density and thickness, as well as improving patient satisfaction.However, no significant difference was observed between the two groups [11].

Erosive oral lichen planus
Out of the 2888 patients included in the study, 20 patients (0.7%) were diagnosed with erosive oral lichen planus and received interventions.The only modality investigated in this group was PRP injection.

PRP
The only study conducted to investigate regenerative medicine in the treatment of erosive oral lichen planus focused on comparing PRP and triamcinolone injection.The results indicated the significant effectiveness of both methods in healing the lesions, and no significant difference was observed between the two groups [15].

Dystrophic epidermolysis bullosa
Out of the 2888 patients included in the study, 14 patients (0.5%) were diagnosed with dystrophic epidermolysis bullosa and received interventions.The only modality investigated in this group was intravenous injection of mesenchymal stem cells.

Intra venous injection of mesenchymal stem cells
The only study conducted to investigate regenerative medicine in the treatment of dystrophic epidermolysis bullosa focused on comparing intravenous injection of mesenchymal stem cells with a combination of intravenous injection of mesenchymal stem cells and cyclosporine suspension.The results indicated the significant effectiveness of both methods in decreasing the number of new blisters and promoting the healing rate of new blisters, with no significant difference observed between the two groups [17].

Discussion
Regenerative medicine has emerged as a promising field in dermatology, offering innovative therapeutic approaches for various skin conditions.One of the key techniques utilized in regenerative medicine is plateletrich plasma (PRP) injections, which have shown positive results in the treatment of conditions such as hair loss, pigment disorders, and inflammatory skin conditions.One potential way PRP aids in healing inflammatory skin lesions is by releasing a variety of growth factors, such as platelet-derived growth factor (PDGF) and TGF-β, from alpha platelet granules.This increase in TGF-β levels can then trigger negative feedback within the signaling pathways involved in inflammation [1].
In the realm of hair loss, particularly androgenetic alopecia (AGA), PRP injections have been extensively studied [5,20,22].Research suggests that PRP injections, especially when administered using the double spin method, can lead to increased hair growth and density, particularly of terminal hairs [25].Additionally, combining PRP with growth factors such as basic fibroblast growth factor or Concentrated Growth Factor (CGF) has shown enhanced efficacy in promoting hair regrowth [40,43].
In other dermatologic conditions like melasma, regenerative approaches using PRP have yielded positive results.Studies have shown that PRP treatments can lead to significant improvements in skin pigmentation compared to traditional treatments like hydroquinone [12,68].Furthermore, the use of alternative sources of mesenchymal stem cells, such as umbilical cord-derived cells, has shown promising effects in treating melasma [69].
Notably, regenerative techniques like adipose-derived stem cell treatments and PRP injections have also shown potential benefits in addressing skin disorders like lichen sclerosis et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and alopecia areata.Studies have demonstrated the effectiveness of these methods in controlling symptoms, promoting hair growth, and improving patient satisfaction [11,13,14,17,67,70].
Overall, regenerative medicine presents a wide array of therapeutic options for dermatologic conditions, with ongoing research focusing on optimizing treatment protocols and enhancing patient outcomes in the field of dermatology.

Conclusion
Regenerative medicine, as a new branch of medical science, plays an effective role in treating degenerative skin diseases.While this treatment is effective, it has not been associated with serious side effects for patients.Our conclusion in this systematic review study was limited to primary skin diseases, and secondary conditions such as burn scars, acne scars, diabetic wounds, etc., were not investigated.One limitation of our study was the limited access to the complete texts of certain articles.Additionally, our focus was solely on RCTs in this research, and we excluded both case reports and case series from our analysis.It is recommended to conduct more clinical trial studies to explore further the role of regenerative medicine in treating skin diseases.

Fig. 1
Fig. 1 PRISMA chart of studied articles